{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:53:20Z","timestamp":1777424000590,"version":"3.51.4"},"reference-count":47,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p>Regulation of vascular tone and blood flow involves interactions between numerous local and systemic vascular control signals, many of which are altered by Type 2 diabetes (T2D). Vascular responses to endothelin-1 (ET-1) are mediated by endothelin type A (ET<jats:sub>A<\/jats:sub>) and type B (ET<jats:sub>B<\/jats:sub>) receptors that have been implicated in cross talk with \u03b1<jats:sub>1<\/jats:sub>-adrenoceptors (\u03b1<jats:sub>1<\/jats:sub>-AR). ET<jats:sub>A<\/jats:sub>and ET<jats:sub>B<\/jats:sub>receptor expression and plasma ET-1 levels are elevated in T2D; however, whether this influences coronary \u03b1<jats:sub>1<\/jats:sub>-AR function has not been examined. Therefore, we examined the effect of ET<jats:sub>A<\/jats:sub>and ET<jats:sub>B<\/jats:sub>receptor inhibition on coronary vasoconstriction to ET-1 and \u03b1<jats:sub>1<\/jats:sub>-AR activation in a mouse model of T2D. Coronary vascular responses were examined in isolated mouse hearts from control and diet-induced T2D C57BL\/6J mice. Responses to ET-1 and the selective \u03b1<jats:sub>1<\/jats:sub>-AR agonist phenylephrine (PE) were examined alone and in the presence of the nitric oxide synthase inhibitor N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine methyl ester (l-NAME) alone or in combination with selective ET<jats:sub>A<\/jats:sub>or ET<jats:sub>B<\/jats:sub>receptor inhibitors BQ-123 and BQ-788, respectively. Vasoconstriction to ET-1 was enhanced, whereas ET<jats:sub>B<\/jats:sub>, but not ET<jats:sub>A<\/jats:sub>, receptor blockade reduced basal coronary tone in T2D hearts. In the presence of l-NAME, ET<jats:sub>A<\/jats:sub>receptor inhibition attenuated ET-1 vasoconstriction in both groups, whereas ET<jats:sub>B<\/jats:sub>inhibition abolished this response only in control hearts. In addition, ET<jats:sub>A<\/jats:sub>inhibition enhanced \u03b1<jats:sub>1<\/jats:sub>-AR-mediated vasoconstriction in T2D, but not control, hearts following l-NAME treatment. Therefore, in this model, enhanced coronary ET-1 responsiveness is mediated primarily through smooth muscle ET<jats:sub>B<\/jats:sub>receptors, whereas the interaction with \u03b1<jats:sub>1<\/jats:sub>-ARs is mediated solely through the ET<jats:sub>A<\/jats:sub>receptor subtype.<\/jats:p>","DOI":"10.1152\/ajpheart.00566.2007","type":"journal-article","created":{"date-parts":[[2007,7,28]],"date-time":"2007-07-28T01:10:52Z","timestamp":1185585052000},"page":"H2281-H2288","source":"Crossref","is-referenced-by-count":27,"title":["Altered role of smooth muscle endothelin receptors in coronary endothelin-1 and \u03b1<sub>1<\/sub>-adrenoceptor-mediated vasoconstriction in Type 2 diabetes"],"prefix":"10.1152","volume":"293","author":[{"given":"S. B.","family":"Bender","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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